The miR-371∼373 Cluster Represses Colon Cancer Initiation and Metastatic Colonization by Inhibiting the TGFBR2/ID1 Signaling Axis

Cancer Research
Pit UllmannElisabeth Letellier

Abstract

The vast majority of colorectal cancer-related deaths can be attributed to metastatic spreading of the disease. Therefore, deciphering molecular mechanisms of metastatic dissemination is a key prerequisite to improve future treatment options. With this aim, we took advantage of different colorectal cancer cell lines and recently established primary cultures enriched in colon cancer stem cells, also known as tumor-initiating cells (TIC), to identify genes and miRNAs with regulatory functions in colorectal cancer progression. We show here that metastasis-derived TICs display increased capacity for self-renewal, TGFβ signaling activity, and reduced expression of the miR-371∼373 cluster compared with nonmetastatic cultures. TGFβ receptor 2 (TGFBR2) and aldehyde dehydrogenase A1 (ALDH1A1) were identified as important target genes of the miR-371∼373 cluster. In addition, TGFBR2 repression, either by direct knockdown or indirectly via overexpression of the entire miR-371∼373 cluster, decreased tumor-initiating potential of TICs. We observed significantly reduced in vitro self-renewal activity as well as lowered tumor initiation and metastatic outgrowth capacity in vivo following stable overexpression of the miR-371∼373 cluster in diff...Continue Reading

References

Dec 13, 2000·The Journal of Pathology·R E HewittM Tsoskas
Jun 9, 2004·Developmental Biology·Mi-Ra SuhKye-Seong Kim
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 18, 2006·Cell·Gaorav P Gupta, Joan Massagué
Dec 1, 2007·Proceedings of the National Academy of Sciences of the United States of America·Gaorav P GuptaJoan Massagué
Oct 11, 2011·Cell Stem Cell·Sebastian M DieterHanno Glimm
Sep 21, 2012·Nature Reviews. Molecular Cell Biology·Joan Massagué
Oct 19, 2013·Cancer Cell·Sakari Vanharanta, Joan Massagué
Nov 14, 2013·World Journal of Gastroenterology : WJG·Federico CoccoliniFausto Catena
Nov 19, 2013·Oncogene·X SunR G Pestell
Dec 11, 2013·The Journal of Experimental Medicine·Fiorenza LottiJeremy N Rich
Jan 21, 2014·Nature Reviews. Cancer·Anna LasorellaAntonio Iavarone
Mar 13, 2014·Cell Stem Cell·Thordur OskarssonJoan Massagué
Apr 22, 2014·Annals of Surgical Oncology·Kohei NakataMasao Tanaka
Jul 16, 2014·British Journal of Cancer·E LetellierS Haan
Dec 20, 2014·Cancer Letters·Yu XuanYuquan Wei
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
May 21, 2015·Journal of Translational Medicine·Furong WeiJunfu Wang
Jul 17, 2015·Anti-cancer Agents in Medicinal Chemistry·Jing YuXinguo Zhu
Sep 1, 2015·Cancer Letters·Xia XuKai Wang
Apr 17, 2016·Genes & Development·Toni Celià-Terrassa, Yibin Kang
May 26, 2016·EMBO Molecular Medicine·Evelyn FesslerJan Paul Medema
Jul 2, 2016·Cell·M Angela NietoJean Paul Thiery
Aug 19, 2016·British Journal of Cancer·Claudia BellomoAristidis Moustakas
Oct 13, 2017·British Journal of Cancer·Elisabeth LetellierSerge Haan
Oct 19, 2017·The American Journal of Pathology·Futoshi KawamataAkinobu Taketomi

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Citations

Jan 15, 2019·Current Pharmaceutical Design·Reyhaneh Moradi-MarjanehSeyed H Aghaee-Bakhtiari
Jul 6, 2019·Journal of Cellular and Molecular Medicine·Yanyan ChiYan Sun
Dec 25, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Benjiao GongZhaohua Gong
Mar 27, 2020·Frontiers in Cell and Developmental Biology·Madalina Gabriela BarbuSilviu Cristian Voinea
Jan 27, 2019·Journal of Cellular Physiology·Atena SoleimaniSeyed Mahdi Hassanian
Dec 20, 2020·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Kegui ZhangXiaohua Yan
Feb 11, 2021·International Journal of Molecular Sciences·Andrea AngiusMaria Rosaria De Miglio
Dec 17, 2020·International Journal of Molecular Sciences·Shu-Chun LinKuo-Wei Chang

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